Aggravation of Allergic Airway Inflammation by Cigarette Smoke in Mice Is CD44-Dependent

Abstract

BackgroundAlthough epidemiological studies reveal that cigarette smoke (CS) facilitates the development and exacerbation of allergic asthma, these studies offer limited information on the mechanisms involved. The transmembrane glycoprotein CD44 is involved in cell adhesion and acts as a receptor for hyaluronic acid and osteopontin. We aimed to investigate the role of CD44 in a murine model of CS-facilitated allergic airway inflammation.MethodsWild type (WT) and CD44 knock-out (KO) mice were exposed simultaneously to house dust mite (HDM) extract and CS. Inflammatory cells, hyaluronic acid (HA) and osteopontin (OPN) levels were measured in bronchoalveolar lavage fluid (BALF). Proinflammatory mediators, goblet cell metaplasia and peribronchial eosinophilia were assessed in lung tissue. T-helper (Th) 1, Th2 and Th17 cytokine production was evaluated in mediastinal lymph node cultures.ResultsIn WT mice, combined HDM/CS exposure increased the number of inflammatory cells and the levels of HA and OPN in BALF and Th2 cytokine production in mediastinal lymph nodes compared to control groups exposed to phosphate buffered saline (PBS)/CS, HDM/Air or PBS/Air. Furthermore, HDM/CS exposure significantly increased goblet cell metaplasia, peribronchial eosinophilia and inflammatory mediators in the lung. CD44 KO mice exposed to HDM/CS had significantly fewer inflammatory cells in BALF, an attenuated Th2 cytokine production, as well as decreased goblet cells and peribronchial eosinophils compared to WT mice. In contrast, the levels of inflammatory mediators were similar or higher than in WT mice.ConclusionWe demonstrate for the first time that the aggravation of pulmonary inflammation upon combined exposure to allergen and an environmental pollutant is CD44-dependent. Data from this murine model of concomitant exposure to CS and HDM might be of importance for smoking allergic asthmatics.

The Effect of Flavored E-cigarettes on Murine Allergic Airways Disease

“…Using an identical study design, Kumar et al . 53 reported that tobacco cigarette smoke increased HDM-induced airway eosinophils, neutrophils and mucous metaplasia, although effects on AHR did not reach significance. Similarly, concurrent exposure to ovalbumin and tobacco cigarette smoke contributes to more severe allergic airways inflammation, due to effects on eosinophils and neutrophils, and AHR 54 .…”

“…54 used four exposures/day, and Kumar et al . 53 used three exposures/day. Therefore, it is possible that the lack of effect of e-cigarettes with nicotine on AHR and airway remodeling in the present study is due to reduced exposure compared to these tobacco mouse models.…”

Nuclear functions of mammalian MicroRNAs in gene regulation, immunity and cancer

“…CD44, a transmembrane glycoprotein, plays a vital role in a variety of immune processes including lymphocyte activation, cell proliferation and assembly of inflammatory cells. Recently, some studies [ 89 , 90 ] demonstrated that CD44 is associated with airway inflammation, particularly asthma, where Li et al [ 91 ] found high expression level of miR-31 in asthma patients. Further study revealed that miR-31 can directly bind to the promoter of CD44 gene and upregulate its expression.…”

Ezrin Orchestrates Signal Transduction in Airway Cells

“…CD44 is a transmembrane glycoprotein that is highly expressed on the surface of both immune and epithelial airway cells, and its expression is increased in the bronchial epithelium of asthmatic patients (Isacke and Yarwood 2002; Kumar et al 2016; Lackie et al 1997). However, CD44 expression is decreased in the airway smooth muscle cells of asthma and chronic obstructive pulmonary disease (COPD) patients, as shown by RT-PCR and Western blot analyses (Klagas et al 2009).…”